Hering-Breuer Inflation Reflex Research Articles

Inhibitory effect of sulfur dioxide inhalation on Hering-Breuer inflation reflex in mice: role of voltage-gated potassium channels.

Slowly adapting receptors (SARs), vagal mechanosensitive receptors located in the lung, play an important role in regulating the breathing pattern and Hering-Breuer inflation reflex (HBIR). Inhalation of high concentration of sulfur dioxide (SO2), a common environmental and occupational air pollutant, has been shown to selectively block the SAR activity in rabbits, but the mechanism underlying this inhibitory effect remained a mystery. We carried out this study to determine if inhalation of SO2 can inhibit the HBIR and change the eupneic breathing pattern, and to investigate further a possible involvement of voltage-gated K+ channels in the inhibitory effect of SO2 on these vagal reflex-mediated responses. Our results showed 1) inhalation of SO2 (600 ppm; 8 min) consistently abolished both the phasic activity of SARs and their response to lung inflation in anesthetized, artificially ventilated mice, 2) inhalation of SO2 generated a distinct inhibitory effect on the HBIR and induced slow deep breathing in anesthetized, spontaneously breathing mice, and these effects were reversible and reproducible in the same animals, 3) This inhibitory effect of SO2 was blocked by pretreatment with 4-aminopyridine (4-AP), a nonselective blocker of voltage-gated K+ channel, and unaffected by pretreatment with its vehicle. In conclusion, this study suggests that this inhibitory effect on the baseline breathing pattern and the HBIR response was primarily mediated through the SO2-induced activation of voltage-gated K+ channels located in the vagal bronchopulmonary SAR neurons.NEW & NOTEWORTHY This study demonstrated that inhaled sulfur dioxide completely and reversibly abolished the activity of vagal bronchopulmonary slowly adapting receptors, significantly inhibited the apneic response to lung inflation, and induced slow deep breathing in anesthetized mice. More importantly, our results further suggested that this inhibitory effect was mediated through an action of sulfur dioxide and its derivatives on the voltage-gated potassium channels expressed in the slowly adapting receptor sensory neurons innervating the lung.

Bifurcation of the respiratory response to lung inflation in anesthetized dogs

Numerous studies have demonstrated the effect of lung volume on prolongation of duration of expiration (TE) with limited understanding of the TE shortening and termination of expiration as observed in newborn. In 14 dogs, the effects of varied onset of lung inflation during expiration on the TE were evaluated. When lung inflation was applied in the first part of expiration (20–60% of TE) TE was lengthened. However, in the second portion (60–80% of TE) of expiration, lung inflation either terminated or prolonged TE; whereas in the last portion of expiration (80–90% of TE), lung inflation tended to terminate expiration prematurely. The effects were abolished after bilateral vagotomy. We postulate that prolongation of TE relates to the Breuer-Hering inflation reflex, which increases the time needed for a passive expiration; whereas the ability to shorten TE could relate to Head’s paradoxical reflex acting to initiate inspiration or to activate inspiratory motor activity to brake expiratory flow as occurs in the newborn.

Vagal Control of Breathing Pattern after Midcervical Contusion in Rats.

The present study was designed to establish a midcervical contusion model that can simulate long-term respiratory deficits, and investigate the breathing pattern during vagal-mediated respiratory reflexes following midcervical contusion. Moderate and severe (impactor height: 6.25 or 12.5 mm) contusion was induced at midline C3-4 spinal cord in adult Sprague-Dawley rats. The ventilatory behaviors of unanesthetized were evaluated by whole body plethysmography at 1 day and 1, 2, 4, and 8 weeks post-injury. The tidal volume was decreased and frequency was increased in contused animals compared with uninjured animals at the acute injury state. At 8 weeks post-injury, respiratory frequency was similar between groups; however, contused animals had lower tidal volume. The pulmonary chemoreflex induced by intrajugular capsaicin (1.5 μg/kg) injection and the Hering-Breuer inflation reflex induced by increasing positive end-expired pressure (9 cm H2O) were evoked in anesthetized animals at 3 days, or 2 or 8 weeks post-surgery. The result showed that capsaicin induced a significant prolongation of the expiratory duration in uninjured animals; however, this response was greatly attenuated in contused animals at 3 days post-injury. Increased positive end-expired pressure also caused an increase in the expiratory duration in uninjured and moderately contused animals; however, severely contused animals exhibited an attenuated response. At 2 and 8 weeks post-injury, both the pulmonary chemoreflex and the Hering-Breuer inflation reflex were similar between uninjured and contused animals. These data suggested that midcervical contusion can cause a long-term respiratory impairment and a transiently attenuation of vagal-mediated respiratory reflexes.

Learning to breathe: Habituation of Hering–Breuer inflation reflex emerges with postnatal brainstem maturation

The Hering–Breuer (HBR) reflex is considered a major regulatory feedback for the generation and patterning of respiratory activity. While HBR is important in neonates, its significance in adults is controversial. Previous experiments that investigated the plasticity of entrainment of the respiratory rhythm by vagal input demonstrated postnatal changes in HBR plasticity. Here we analyzed postnatal changes in the plasticity of HBR by mimicking the classic lung inflation tests with repetitive tonic vagal stimulation across different postnatal stages in an in situ perfused brainstem preparation of rat. The study shows that neonates stereotypically exhibit HBR stimulus-dependent prolongation of expiration while juvenile preparations (>postnatal day 16) showed significant habituation of HBR following repetitive stimulation. Subsequent experiments employing physiological lung inflation tests in situ confirmed HBR habituation in juveniles. We conclude that postnatal emergence of HBR habituation explains the weak contribution and high activation threshold of HBR in the regulation of eupnea.

Role of Inhibition in Respiratory Pattern Generation

Postsynaptic inhibition is a key element of neural circuits underlying behavior, with 20-50% of all mammalian (nongranule) neurons considered inhibitory. For rhythmic movements in mammals, e.g., walking, swimming, suckling, chewing, and breathing, inhibition is often hypothesized to play an essential rhythmogenic role. Here we study the role of fast synaptic inhibitory neurotransmission in the generation of breathing pattern by blocking GABA(A) and glycine receptors in the preBötzinger complex (preBötC), a site essential for generation of normal breathing pattern, and in the neighboring Bötzinger complex (BötC). The breathing rhythm continued following this blockade, but the lung inflation-induced Breuer-Hering inspiratory inhibitory reflex was suppressed. The antagonists were efficacious, as this blockade abolished the profound effects of the exogenously applied GABA(A) receptor agonist muscimol or glycine, either of which under control conditions stopped breathing in vagus-intact or vagotomized, anesthetized, spontaneously breathing adult rats. In vagotomized rats, GABA(A)ergic and glycinergic antagonists had little, if any, effect on rhythm. The effect in vagus-intact rats was to slow the rhythm to a pace equivalent to that seen after suppression of the aforementioned Breuer-Hering inflation reflex. We conclude that postsynaptic inhibition within the preBötC and BötC is not essential for generation of normal respiratory rhythm in intact mammals. We suggest the primary role of inhibition is in shaping the pattern of respiratory motor output, assuring its stability, and in mediating reflex or volitional apnea, but not in the generation of rhythm per se.

Influence of age, body temperature, GABAA receptor inhibition and caffeine on the Hering–Breuer inflation reflex in unanesthetized rat pups

We measured the duration of apnea induced by sustained end-inspiratory lung inflation (the Hering Breuer Reflex, HBR) in unanesthetized infant rat pups aged 4 days (P4) to P20 at body temperatures of 32°C and 36°C. The expiratory prolongation elicited by the HBR lasted longer in the younger pups and lasted longer at the higher body temperature. Blockade of adenosine receptors by caffeine following injection into the cisterna magna (ICM) significantly blunted the thermal prolongation of the HBR. Blockade of gama-amino-butyric acid A (GABAA) receptors by pre-treatment with ICM bicuculline had no effect on the HBR duration at either body temperature. To test the hypothesis that developmental maturation of GABAergic inhibition of breathing was modifying the response to bicuculline, we pretreated rat pups with systemically administered bumetanide to lower the intracellular chloride concentration, and repeated the bicuculline studies. Bicuculline still did not alter the HBR at either temperature after bumetanide treatment. We administered PSB-36, a selective adenosine A1 receptor antagonist, and this drug treatment did not modify the HBR. We conclude that caffeine blunts the thermal prolongation of the HBR, probably by blocking adenosine A2a receptors. The thermally sensitive adenosinergic prolongation of the HBR in these intact animals does not seem to depend on GABAA receptors.

Lipopolysaccharide-induced fever alters Hering–Breuer reflex in anesthetized rats

The aim of the study was to test the hypothesis that control of breathing via Hering–Breuer reflex (HB) is influenced by lipopolysaccharide (LPS)-induced fever in rats. Animals were injected intraperitoneally with LPS and control group with an equivalent volume of saline. HB reflex was elicited by inflations of the lungs followed by occlusion of the airways under control of esophageal pressure. Duration of HB reflex (Tapnoe) was continuously reduced as body temperature rose during experiment. Compared to normothermic controls, animals with fever had significant shortening of Tapnoe at 240min and 300min after LPS administration. Fever was further accompanied by a reduction in the strength of HB reflex (inhibitory ratio, IR). In comparison with controls, significant decrease of IR was observed at 300min after LPS injection. Conclusion: altered neural control of breathing demonstrated by decreased power of Hering–Breuer inflation reflex in conditions of LPS-induced fever may facilitate thermal tachypnoea and/or play a role in the origin of respiratory instability accompanying febrile response.

Thermal prolongation of the Hering‐Breuer inflation reflex in neonatal rats depends on an adenosinergic mechanism in the brainstem

The Hering‐Breuer (HB) inflation reflex prolongs expiratory duration (TE), and elevated body temperature increases this prolongation in neonatal rats. The neurophysiological mechanisms of this thermal sensitivity have not been studied, but the thermal sensitivity of the HB reflex is similar to that of the laryngeal chemoreflex (LCR). Therefore, we tested the hypothesis that blocking adenosine receptors with caffeine, which shortens the LCR, would blunt the thermal prolongation of apnea associated with the HB reflex. Neonatal rats (P4 to P20) were anesthetized briefly to administer intracisternal caffeine (2 microL of 10 mM) or vehicle, allowed to wake up and studied in a head out plethysmograph. The HB reflex was elicited at body temperatures of 32 and 36 degrees C by decreasing the plethysmographic pressure (−5 cm H2O) at the end of inspiration. The inflation was maintained until the next inspiratory effort, and we measured the apneic interval between inspiratory efforts. Intracisternal injection of caffeine shortened the HB reflex apnea at the higher body temperature, and the shortening was greater in younger animals.Support: grants 36379 & 42707 from the NICHD.

Suppression of the cough reflex by inhibition of ERK1/2 activation in the caudal nucleus tractus solitarii of the rabbit

The caudal nucleus tractus solitarii (cNTS), the predominant site of termination of cough-related afferents, has been shown to be a site of action of some centrally acting antitussive agents. A role of ERK1/2 has been suggested in acute central processing of nociceptive inputs. Because pain and cough share similar features, we investigated whether ERK1/2 activation could also be involved in the central transduction of tussive inputs. For this purpose, we undertook the present research on pentobarbital sodium-anesthetized, spontaneously breathing rabbits by using microinjections (30-50 nl) of an inhibitor of ERK1/2 activation (U0126) into the cNTS. Bilateral microinjections of 25 mM U0126 caused rapid and reversible reductions in the cough responses induced by both mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. In particular, the cough number and peak abdominal activity decreased. Bilateral microinjections of 50 mM U0126 completely suppressed the cough reflex without affecting the Breuer-Hering inflation reflex, the pulmonary chemoreflex, and the sneeze reflex. These U0126-induced effects were, to a large extent, reversible. Bilateral microinjections of 50 mM U0124, the inactive analog of U0126, at the same cNTS sites had no effect. This is the first study that provides evidence that ERK1/2 activation within the cNTS is required for the mediation of cough reflex responses in the anesthetized rabbit. These results suggest a role for ERK1/2 in the observed effects via nontranscriptional mechanisms, given the short time involved. They also may provide hints for the development of novel antitussive strategies.

Habituation without NMDA Receptor-Dependent Desensitization of Hering–Breuer Apnea Reflex in a Mecp2+/− Mutant Mouse Model of Rett Syndrome

Non-associative learning is a basic neuroadaptive behavior exhibited in almost all animal species and sensory modalities but its functions and mechanisms in the mammalian brain are poorly understood. Previous studies have identified two distinct forms of non-associative learning in the classic Hering–Breuer inflation reflex (HBIR) induced apnea in rats: NMDA receptor (NMDAR)-independent habituation in a primary vagal pathway and NMDAR-dependent desensitization in a secondary pontine pathway. Here, we show that abnormal non-associative learning of the HBIR may underlie the endophenotypic tachypnea in an animal model of Rett syndrome (RTT), an autism-spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). Mecp2+/− symptomatic mice on a mixed-strain background demonstrated significantly increased resting respiratory frequency with shortened expiration and normal inspiratory duration compared with asymptomatic mutants and wild-type controls, a phenotype that is characteristic of girls with RTT. Low-intensity electrical stimulation of the vagus nerve elicited fictive HBIR with time-dependent habituation in both Mecp2+/− and wild-type mice. However, time-dependent desensitization of the HBIR was evidenced only in wild-type controls and asymptomatic mutant mice but was absent or suppressed in Mecp2+/− symptomatic mice or in wild-type mice after blockade of NMDAR with dizocilpine. Remarkably, ∼50% of the Mecp2+/− mice developed these X-linked phenotypes despite somatic mosaicism. Such RTT-like respiratory endophenotypes in mixed-strain Mecp2+/− mice differed from those previously reported in Mecp2-/y mice on pure C57BL/6J background. These findings provide the first evidence indicating that impaired NMDAR-dependent desensitization of the HBIR may contribute to the endophenotypic tachypnea in RTT.

Mechanisms of the Respiratory Activity of Leptin at the Level of the Solitary Tract Nucleus

Acute experiments on anesthetized laboratory rats were performed to study the effects microinjections of 10(-4) M leptin into the solitary tract nucleus on the extent of the Hering-Breuer inflation reflex in ventilatory reactions to hypercapnia. Local administration of leptin into this area led to inhibition of the Hering-Breuer reflex. The extent of ventilatory responses to hypercapnia, conversely, increased, which may provide evidence that leptin has a modulatory influence on central chemoreceptors. These physiological mechanisms of action probably play a leading role in mediating the stimulatory respiratory effects of leptin at the level of the solitary tract nucleus.

Severe spontaneous bradycardia associated with respiratory disruptions in rat pups with fewer brain stem 5-HT neurons

The medullary 5-HT system has potent effects on heart rate and breathing in adults. We asked whether this system mitigates the respiratory instability and bradycardias frequently occurring during the neonatal period. 5,7-Dihydroxytryptamine (5,7-DHT) or vehicle was administered to rat pups at postnatal day 2 (P2), and we then compared the magnitude of bradycardias occurring with disruptions to eupnea in treated and vehicle control littermates at P5-6 and P10-12. We then used a novel method that would allow accurate assessment of the ventilatory and heart rate responses to near square-wave challenges of hypoxia (10% O2), hypercapnia (5 and 8% CO2 in normoxia and hyperoxia), and asphyxia (8% CO2-10% O2), and to the induction of the Hering-Breuer inflation reflex (HBR), a potent, apnea-inducing reflex in newborns. The number of 5-HT-positive neurons was reduced approximately 80% by drug treatment. At both ages, lesioned animals had considerably larger bradycardias during brief apnea; at P5-6, average and severe events were approximately 50% and 70% greater, respectively, in lesioned animals (P = 0.002), whereas at P10-12, events were approximately 23% and 50% greater (P = 0.018). However, lesioning had no effect on the HR responses to sudden gas challenge or the HBR. At P5-6, lesioned animals had reduced breathing frequency and ventilation (Ve), but normal Ve relative to metabolic rate (Ve/Vo2). At P10-12, lesioned animals had a more unstable breathing pattern (P = 0.04) and an enhanced Ve response to moderate hypercapnia (P = 0.007). Within the first two postnatal weeks, the medullary 5-HT system plays an important role in cardiorespiratory control, mitigating spontaneous bradycardia, stabilizing the breathing pattern, and dampening the hypercapnic Ve response.

Use‐dependent learning and memory of the Hering–Breuer inflation reflex in rats

The classic Hering-Breuer inflation reflex (HBIR) is a widely held tenet for understanding the lung volume-related vagal control of respiratory rhythm. Recent evidence, however, has revealed that the fictive HBIR elicited by electrical vagal stimulation in rats is not static but may be attenuated centrally by two forms of non-associative learning (habituation and desensitization) that continually mitigate the reflex effects with exponential adaptations like a differentiator or high-pass filter. Desensitization is analogous to habituation but exhibits an explicit short-term memory (STM) in the form of a rebound response with exponential decay during recovery from stimulation. To investigate whether such learning and memory effects are lung volume related and use-dependent (practice makes perfect), we compared the time-dependent changes in inspiratory and expiratory durations (t(I) and t(E)) during and after 1 or 8 min unilateral lung inflation or high-frequency, low-intensity vagal stimulation in anaesthetized, uni- or bi-vagotomized rats. Unilateral lung inflation and vagal stimulation both elicited abrupt shortening of t(I) and lengthening of t(E) (HBIR effects) and gradual habituation and desensitization throughout the 1 or 8 min test period, followed by rebound responses in t(I) and t(E) with exponential recovery (STM effects) in the post-test period. In both cases, the STM time constants for t(I) and t(E) were significantly longer with the 8 min test than with the 1 min test (17-45 versus 4-11 s, P < 0.01). We conclude that the HBIR and its central habituation and desensitization are mediated peripherally by lung volume-related vagal afferents, and that the STM of desensitization is use-dependent. The translational implications of these findings are discussed.

Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary stretch receptor (Breuer–Hering) reflex pathway

The Breuer–Hering inflation reflex is initiated by activation of the slowly adapting pulmonary stretch receptor afferents (SARs), which monosynaptically activate second-order relay neurones in the dorsal medullary nucleus of the solitary tract (NTS). Here we demonstrate that during lung inflation SARs release both ATP and glutamate from their central terminals to activate these NTS neurones. In anaesthetized and artificially ventilated rats, ATP- and glutamate-selective microelectrode biosensors placed in the NTS detected rhythmic release of both transmitters phase-locked to lung inflation. This release of ATP and glutamate was independent of the centrally generated respiratory rhythm and could be reversibly abolished during the blockade of the afferent transmission in the vagus nerve by topical application of local anaesthetic. Microionophoretic application of ATP increased the activity of all tested NTS second-order relay neurones which receive monosynaptic inputs from the SARs. Unilateral microinjection of ATP into the NTS site where pulmonary stretch receptor afferents terminate produced central apnoea, mimicking the effect of lung inflation. Application of P2 and glutamate receptor antagonists (pyridoxal-5′-phosphate-6-azophenyl-2′,4′-disulphonic acid, suramin and kynurenic acid) significantly decreased baseline lung inflation-induced firing of the second-order relay neurones. These data demonstrate that ATP and glutamate are released in the NTS from the central terminals of the lung stretch receptor afferents, activate the second-order relay neurones and hence mediate the key respiratory reflex — the Breuer—Hering inflation reflex.

Breathing Patterns In The Newborn And Related Cardiovascular Adjustments

The transition from foetal to neonatal life is a dramatic one; it demands considerable and effective physiological alteration in the newborn to ensure survival. Simultaneously cardio-respiratory adjustments are initiated and breathing maintained on a continuous basis. The basic movements in the human foetus being about 8 weeks after conception, and by 12 weeks some of these foetal breathing movements have attained a pattern similar to respiration. At birth also, the regulatory neural network responsible for respiratory control is capable of generating robust rhythm-driven ventilation that can adjust to homeostatic needs. The so far unexplained conversion from episodic to continuous breathing with the onset of birth remains one of the mysteries of perinatal medicine. The initiation and establishment of breathing is of paramount importance to the survival of the newborn. Normal breathing requires pre-Botzinger complex neuro-kinin-1 receptor-expressing neurons. Some respiratory reflexes have been demonstrated in the newborn that control respiration. One of such is the Hering-Breuer Inflation Reflex (HBIR). The conversion from intrauterine to extrauterine life is accompanied by adjustments in virtually every organ system but the focus of this review is on that of the respiratory system and its effects on the cardiovascular system. These changes ensure that the newborn adjusts quietly and uniquely to its new environment at birth. Keywords: Breathing patterns, newborn, cardiovascular adjustments.Journal of Mining and Geology Vol. 5 (1&2) 2006: pp. 23-35

The role of excitatory amino acids and substance P in the mediation of the cough reflex within the nucleus tractus solitarii of the rabbit

We hypothesized that cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit is primarily mediated by glutamatergic neurotransmission at the level of the caudal portions of the medial subnucleus of the nucleus tractus solitarii (NTS) and the lateral commissural NTS where cough-related afferents terminate, and that this reflex is potentiated by local release of substance P. To test our hypothesis, we performed bilateral microinjections (30–50 nl) of ionotropic glutamate receptor antagonists or substance P into these locations in pentobarbitone anaesthetized, spontaneously breathing rabbits. Blockade of NMDA and non-NMDA receptors by 50 mM kynurenic acid abolished the cough reflex without affecting the Breuer–Hering inflation reflex or the pulmonary chemoreflex. Blockade of non-NMDA receptors using 10 mM CNQX or 5 mM NBQX caused identical effects. Blockade of NMDA receptors by 10 mM D-AP5 strongly reduced, but did not abolish cough responses. Microinjections of 1 mM substance P increased peak and rate of rise of abdominal muscle activity as well as cough number. These results are the first to provide evidence that ionotropic glutamate receptors, especially non-NMDA receptors, located within specific regions of NTS are primarily involved in the mediation of cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit. Present findings on substance P cough-enhancing effects extend previous observations and are relevant to the tachykinin-mediated central sensitization of the cough reflex. They also may provide hints for further studies on centrally acting antitussive drugs.

The effects of positioning on the Hering‐Breuer reflex in the preterm infant

The aim of this study was to determine the effect of positioning on the Hering-Breuer inflation reflex (HBIR) in the preterm infant. Seven, non-intubated, premature infants, ranging in birthweight from 732 to 1450 g with post-conceptual ages of 32-36 weeks were studied. In each infant, pulmonary function testing, including the HBIR was obtained using the SensorMedics 2600 during quiet sleep in the supine and prone position. The strength of the HBIR was quantified by the measurement of the percent prolongation of expiration after an occluded breath. Sleep states were categorized by the criteria of Prechtl. There was a significant difference in Hering-Breuer activity in the prone position versus the supine position with a consistently stronger reflex in the prone position. The mean percent prolongation of expiration was 237 +/- 108% in the prone position versus 95 +/- 32% in the supine position. Analysis of the data, using paired t-testing revealed a mean difference of 142 +/- 119% between prone and supine positions (P=0.028). Significant differences in the strength of the HBIR occur in relation to positioning in the preterm infant. Newborn positioning may affect pulmonary reflexes and may play a role in control of breathing.

Ionotropic glutamate receptors mediate excitatory drive to caudal medullary expiratory neurons in the rabbit

Most of the neurons of the caudal ventral respiratory group (cVRG) are bulbospinal expiratory neurons that receive their main excitatory drive from more rostral, but not yet defined regions. This study was devoted to investigate the functional role of ionotropic excitatory amino acid (EAA) receptors in the excitatory drive transmission to cVRG expiratory neurons during eupnoeic breathing and some respiratory reflexes including cough induced by mechanical stimulation of the tracheobronchial tree. The experiments were performed on spontaneously breathing rabbits under pentobarbitone anesthesia making use of microinjections (30–50 nl) of EAA receptor antagonists into the cVRG. Phrenic nerve and abdominal muscle activities were recorded. Bilateral microinjections of 50 mM kynurenic acid (KYN), a broad-spectrum EAA antagonist, and 10 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA antagonist, or 5 mM 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX), a more specific non-NMDA antagonist, completely suppressed spontaneous rhythmic abdominal activity and reflex expiratory responses either to tracheal occlusion at end-inspiration (Breuer–Hering inflation reflex) or to expiratory threshold loading (5 cm H 2O); they also suppressed both the inspiratory and expiratory components of the cough reflex. Spontaneous rhythmic abdominal activity and the reflex respiratory responses were strongly reduced, but not completely abolished by microinjections of 10 mM d(−)-2-amino-5-phosphonopentanoic acid (D-AP5), an NMDA antagonist. The results provide evidence that the excitatory drive to cVRG bulbospinal expiratory neurons during eupnoeic breathing and the investigated respiratory reflexes is mediated by EAA receptors. They also support the view that neurons located in the cVRG are not merely elements of the expiratory output system.

Henry Head and his paradoxical reflex.

Henry Head and his paradoxical reflex.

Hering-Breuer reflex and sleep state in the preterm infant.

The aim of this study was to determine the effect of sleep state on the Hering-Breuer inflation reflex in the preterm infant. Seventeen nonintubated, premature infants, ranging in birth weight from 980-2,440 g with postconceptual ages of 30-36 weeks, were studied. In each infant, pulmonary function testing, including the Hering-Breuer inflation reflex, was obtained using the SensorMedics 2600 during active and quiet sleep states in supine position. The strength of the Hering-Breuer inflation reflex was quantified by the measurement of the percent prolongation of expiration after an occluded breath. Sleep states were categorized by the criteria of Prechtl. There was a significant difference in Hering-Breuer activity in active (REM) vs. quiet (non-REM) sleep, with a consistently stronger reflex in the active sleep state. The mean percent prolongation of expiration was 419% in active sleep vs. 87% in quiet sleep. Analysis of the data, using a paired t-test, revealed a mean difference of 331 +/- 185% between active and quiet sleep (P = 0.000). In conclusion, significant differences in the strength of the Hering-Breuer inflation reflex occur in relation to sleep state, and may explain the variability of the reflex described in previous studies. Measurement of the Hering-Breuer inflation reflex may be affected by pulmonary stretch receptors as well as chest wall afferents in the preterm infant.